Molecular biology methods, such as those based on the reverse transcription polymerase chain reaction, are also being used for SLN analysis, although they are generally characterized by relatively poor reproducibility, longer time for intraoperative analysis and their inability to analyse the whole of the LNs. The recently developed one step nucleic acid amplification method is currently being validated in many centres [5.86].
5.5. ADDED VALUE OF INTRAOPERATIVE
There is no consensus on the need for intraoperative imaging to help SLN detection in breast cancer patients. Some authors believe that intraoperative imaging using a portable gamma camera is useful only when no conventional gamma camera is available, in particular in cases with extra-axillary drainage [5.89]. Difficult situations can be encountered in cases of intramammary or IMN SLNs, or when the SLN is located very close to the injection site. Although the large majority of these cases can be solved using the presurgical information provided by SPECT/CT, real time images acquired using a portable gamma camera can also be useful. Moreover, the use of point sources (e.g. 133Ba or 125I) facilitates SLN localization, as these sources can be depicted separately on the screen of the portable gamma camera, thus functioning as a pointer in the search for the SLNs. Appropriate use of a portable or a hand-held mini gamma camera enhances the reliability of the gamma probe by adding a clear image of the surgical field. Use of an intraoperative imaging device implies the possibility to better plan the surgical approach, to monitor the lymphatic basin before and after removal of the hot nodes, and to verify the correct SLN excision.
For difficult to retrieve SLNs, real time imaging with this portable gamma camera in combination with the use of a traditional gamma counting probe results in higher intraoperative detection and localization of SLNs, especially when the injection site is close to the lymphatic basin, as in the case of intramammary and IMN SLNs [5.90] (Fig. 5.11).
FIG. 5.11. Pre-operative imaging using a portable gamma camera in a 42 year old patient with a T1 breast cancer in her right upper quadrant. Left: After injecting 111 MBq of 99mTc nanocolloid, a scintigraphic anterior view is acquired by placing the portable gamma camera at previously marked points on the skin (internal mammary chain). Right: Image clearly shows two separate SLNs in this area, of which only the more caudal SLN had been visualized by planar imaging with a conventional gamma camera.
FIG. 5.12. A 57 year old patient with a breast cancer in her left upper outer quadrant.
Lymphoscintigraphic images acquired 2 h after intratumoural injection of 111 MBq of
99mTc nanocolloid, showing two SLNs (yellow circle) (A). Image obtained using a portable gamma camera in the operating room before starting the SLN procedure, showing a similar scintigraphic pattern (yellow arrow) (B). Image acquired using the portable gamma camera after SLN excision, showing completeness of SLN removal (the residual large area of radioactivity accumulation corresponds to retention of the radiocolloid at the intratumoural injection site) (C).
After excision of each hot LN, a new image is acquired and compared with the image acquired before excision (Fig. 5.12). If focal radioactivity remains at the same location, it is concluded that another possible SLN is still in place.
Portable gamma cameras have also been used with promising results in other GOSTT environments regarding breast cancer, such as in the ROLL procedure, to check for tumour involvement of the resection margin [5.91]
(Fig. 5.13).
New technological possibilities include a spatial localization system and two tracking targets to be fixed on the gamma probe, with the traditional acoustic signal of the gamma probe thus being combined with a real time 3-D visualization system available for the surgeon in the operating theatre (see Fig. 5.14). This feature, together with the real time depth information that the system may provide, would expand its application in SLN procedures in oncology, particularly for malignancies with deep lymphatic drainage [5.92].
5.6. ROLL AND OTHER PRIMARY LOCALIZING TECHNIQUES 5.6.1. ROLL
Screening programmes for breast cancer have led to an increase in detection of non-palpable breast tumours. Current approaches to breast cancer surgery aim at removing the lesion with an adequate clearance margin while, at the same
time, accurately assessing the risk of distant metastases. Effective localization procedures are required to ensure complete excision of small non-palpable lesions detected on either symptomatic mammography or screening mammography.
Several localization techniques have been developed for this purpose.
FIG. 5.13. The ROLL technique. After injecting 37 MBq in 0.2 mL of 99mTc MAA into the breast lesion (guided by ultrasonography), the surgeon performed tumour resection under guidance using the hand-held gamma probe. X ray lateral view of the specimen with the reference needle attached to the lesion (A). X ray anterior view of the same specimen (numbers indicate the specimen orientation in clockwise form) (B). Images of the surgical bed and the tumoural specimen were acquired by means of a portable gamma camera, fitted with a pinhole collimator (C, D). A 99mTc pointer was used to draw an outline image around the specimen in the same situation as in the X ray views. Potential involvement of the upper outer margins is suggested, as the injected radiotracer is closer to those margins.
FIG. 5.14. Freehand SPECT based device system used for radioguided surgery in a patient with non-palpable breast cancer. (A) Overlay of freehand SPECT 3-D image on the video display shows high retention of radiocolloid at the intratumoural injection site. (B) After tumour removal, the absence of radioactivity accumulation in the surgical field confirms complete excision of the tumour. (C, D) A similar approach is used to guide the surgeon for complete removal of SLNs (red arrows).
Wire localization of non-palpable lesions has been the most widely used pre-operative technique for many years. Although this is a reasonably effective technique, it involves a number of disadvantages. First, the entry site of the wire is often not at the ideal location for surgical incision at the time of operation.
This may lead to additional unnecessary dissection and suboptimal cosmetic results. In addition, the wire must be placed on the day of the operation, necessitating the coordination of radiology and operative schedules. The most important disadvantage, however, is the inaccuracy of localizing the target lesion percutaneously and during dissection. This results in high rates of reoperation for tissue margins involved in carcinoma.
Intraoperative US imaging without pre-operative wire localization has been used to map excision of non-palpable breast lesions; however, this technique has limitations, as the breast lesion must be visible during the US imaging [5.93–5.95].
The ROLL approach has gained popularity for non-palpable tumour lesions, including breast cancer. ROLL involves the injection into the centre of the lesion of a small amount of radioactive tracer that does not migrate from the site of interstitial injection, typically 99mTc MAA. Injection is performed on the same day or on the day before surgery, under mammographic or US guidance; activity injected ranges from 1.8 MBq (0.05 mCi) to 148 MBq (4 mCi). Surgeons identify the lesion intraoperatively as a hot spot by using a hand-held gamma probe, which allows accurate lesion localization and removal with minimal excision of healthy tissue (Fig. 5.15). After specimen resection, residual activity in the surgical field must be checked to avoid the possibility of missing some residual involved tissue [5.96–5.98]. This technique enables a good cosmetic outcome.
FIG. 5.15. The ROLL surgical technique. (A) The probe assesses the highest activity area.
(B) The ROLL technique does not interfere with the surgical approach (skin incision) as the hookwire approach does (black arrow). (C) The surgeon resects the specimen using gamma probe guidance. (D) After resection, the surgical bed is checked again for any residual activity.
Additional advantages of ROLL versus prior techniques include better lesion concentricity into the resected specimen, better free margins and ease of the entire procedure. However, some potential pitfalls have been described;
these are related to possible radiotracer spillage, contamination of the skin or the injection path or ductal diffusion, as well as the presence of microcalcifications or ductal carcinoma in situ [5.99, 5.100].
A systematic review of the ROLL technique concluded that this approach compares favourably with conventional wire localization for non-palpable breast lesions (Table 5.2) [5.101–5.108]. On the other hand, radiation doses at the injection site, and patient and staff absorbed doses are maintained well within the recommended limits established by the International Commission on Radiological Protection (ICRP) [5.103, 5.109, 5.110]. Finally, the possibility of performing ROLL after systemic intravenous administration of 99mTc sestamibi (as a non-specific, tumour seeking agent) on the day of surgery has also been described [5.111].
TABLE 5.2. SUMMARY OF THE STUDIES COMPARING ROLL VERSUS THE HOOKWIRE TECHNIQUE
Reference n (ROLL–hookwire) Detection (%)
Free margins (ROLL versus hookwire)
(%) p
Gallegos [5.101] 132 (65–67) 100 83 versus 64 0.014
Macmillan et al. [5.102] 95 (48–47) 100 61 versus 72 NS Nadeem et al. [5.103] 130 (65–65) 100 83 versus 57 0.001
Thind et al. [5.104] 140 (70–70) 100 84 versus 60 0.002
Zgajnar et al. [5.105] 143 (51–92) 100 70 versus 44 —
Rönkä et al. [5.106] 78 (64–14) 100 89 versus 79 0.05
Fraile et al. [5.107] 233 (65–168) 100 80 versus 70 NS
Strnad et al. [5.108] 33 (21–12) 100 Hookwire < ROLL NS ROLL: radioguided occult lesion localization.
Reported advantages of the ROLL technique include:
— Precise intraoperative localization of the breast lesion;
— Complete lesion resection, with free margins and reduced need for second operations;
— An increased capacity to centre the lesion within the specimen;
— A surgical approach (skin incision) that is independent from the intralesional radiotracer injection procedure.
5.6.2. Combined SLNB and ROLL procedures
As ROLL is an excellent technique to remove small breast cancers, it is very important to simultaneously perform SLNB without compromising oncological safety and the SLN detection rate. Different techniques have been described to identify the SLNs in combination with ROLL (SNOLL). De Cicco et al. [5.112]
obtained a high sensitivity when combining an intratumoural injection of
99mTc MAA for ROLL of a tumour with a subdermal injection of 99mTc nanocolloid for SLNM and SLNB. When the lesions are located near to the areola, intraoperative interference between the ROLL tracer and SLNM tracer could be avoided by elevation of the dermis and the subdermal area after skin incision.
Other investigators have successfully used a single intratumoural injection for both ROLL and SNOLL in the same session. In the largest retrospective series to date, 959 patients with proven breast cancer underwent ROLL plus radioguided SLNB, with successful breast lesion localization in 99.6% of the cases and negative surgical margins in 91.6% of the cases [5.112, 5.113]. The majority of the studies published so far with this technique show a high percentage of successful tumour resection and intraoperative SLN localization with reduced failure [5.114–5.116].
5.6.3. Radioactive seeds
Alternatives to hookwire localization of occult breast lesions include carbon trace and US guided resection, as well as the use of sealed radioactive seeds. The seed technique was described initially in 2001 by Grey et al. [5.117], based on placement of an 125I titanium seed in the centre of the lesion under mammographic or ultrasonographic guidance. Subsequently, excision of the lesion is guided by a hand-held gamma probe. The seeds are essentially the same as the seeds used in brachytherapy for cancer of the prostate. The 125I radioactive seed is composed of a 4.5–0.8 mm titanium capsule containing a ceramic cylinder enriched with radioiodine. Iodine-125 has a long decay time (half-life of 59.4 d), emitting low energy photons (27 keV). The use of one or two seeds with this low
photon energy has a negligible effect on the surrounding tissue. The non-palpable lesion is visualized by mammography or ultrasonography. The radioactive seed is placed in the breast lesion using an 18 G needle fixed in a needle holder. After successful positioning, the exact location is confirmed by mammography. If a SNOLL technique is scheduled, the 99mTc colloid is injected around the tumour.
Thus, the hand-held gamma probe can be switched between the 27 keV energy window of the 125I source and the 140 keV of the 99mTc, allowing discrimination between these two isotope sources. As in the ROLL technique, the skin incision is made at the site with highest counts, or at a site suitable for oncoplastic breast surgery. Seed removal is verified by the absence of 125I activity in the breast and its presence in the specimen. X rays of the surgical specimen confirm the presence of the seed and the relation of the lesion to the resection margins.
In a study involving 325 patients with non-palpable breast cancer lesions, complete resection was achieved in 95% of the cases [5.118]. The same technique was compared with classical hookwire localization. A second operation was required in 8% of the seed’s group to achieve negative margins, versus 25% in the hookwire group [5.119]. Therefore, radioguided seed localization in non-palpable breast lesions is at least equivalent to the hookwire technique in terms of ease of procedure, removing the target lesion, volume of breast tissue excised, obtaining negative margins, avoiding a second operative intervention and allowing for simultaneous axillary staging [5.120, 5.121].